RGS4, a GTPase activator, improves renal function in ischemia–reperfusion injury

Siedlecki, Andrew; Jin, Xiaohua; Thomas, Winston; Hruska, Keith A.; Muslin, Anthony J.

doi:10.1038/ki.2011.63

Cited by 23 publications

(38 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Components of IRI which contribute to adverse transplant outcomes include inflammation, reactive oxygen species production (ROS), necrosis, apoptosis, and thrombosis (2,3). ROS production, an immediate response to ischemia/reperfusion, triggers or amplifies many downstream processes including vasoconstriction and thrombosis that further deprive the graft organ of oxygen and nutrients.…”

Section: Introductionmentioning

confidence: 99%

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

Lin¹,

Manning²,

Jia³

et al. 2014

Transplantation

View full text Add to dashboard Cite

Background Ischemia/reperfusion injury (IRI) significantly contributes to delayed graft function and inflammation leading to graft loss. IRI is exacerbated by the thrombospondin-1/CD47 system through inhibition of nitric oxide signaling. We postulate that CD47 blockade and prevention of nitric oxide inhibition reduces IRI in organ transplantation. Methods We used a syngeneic rat renal transplantation model of IRI with bilaterally nephrectomized recipients to evaluate the effect of a CD47 monoclonal antibody (CD47mAb) on IRI. Donor kidneys were flushed with CD47mAb OX101 or an isotype-matched control immunoglobulin and stored at 4°C in UW solution for 6 hours prior to transplantation. Results CD47mAb perfusion of donor kidneys resulted in marked improvement in post-transplant survival, lower levels of serum creatinine, BUN, phosphorus and magnesium and less histologic evidence of injury. In contrast, control groups did not survive more than 5 days, had increased biochemical indicators of renal injury and exhibited severe pathological injury with tubular atrophy and necrosis. Recipients of CD47mAb-treated kidneys showed decreased levels of plasma biomarkers of renal injury including cystatin C, osteopontin, TIMP1, β2-microglobulin, VEGF-A and clusterin compared to the control group. Furthermore, laser Doppler assessment showed higher renal blood flow in the CD47mAb-treated kidneys. Conclusions These results provide strong evidence for the use of CD47 antibody-mediated blockade to reduce IRI and improve organ preservation for renal transplantation.

show abstract

Section: Introductionmentioning

confidence: 99%

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

Lin¹,

Manning²,

Jia³

et al. 2014

Transplantation

View full text Add to dashboard Cite

show abstract

“…Nevertheless, in vivo whole animal models are indispensable, because of the limitation of the in vitro models to mimic the complexity of human body (45). Since the 1960s, various animal models of ischemic AKI have been developed and tested, and currently, two kinds of warm renal ischemia-reperfusion (IR) models are mainly used: 1) bilateral renal ischemic reperfusion (IR) (2-6, 8, 13, 14, 17, 19, 22, 23, 25-27, 30, 31, 35, 39, 41-43, 46, 51, 53-57, 59, 61, 63, 67, 68, 75-80) and 2) unilateral renal IR (1,9,15,18,20,21,24,29,33,34,37,38,40,44,50,58,60,62,64,66). Depending on whether the contralateral kidney is removed, the unilateral model can be further divided into two subtypes: unilateral IR with contralateral nephrectomy (15,18,20,29,38,40,44,50) or without contralateral nephrectomy (1,9,21,24,45,60).…”

mentioning

confidence: 99%

Mouse model of ischemic acute kidney injury: technical notes and tricks

Wei

Dong

2012

American Journal of Physiology-Renal Physiology

237

206

View full text Add to dashboard Cite

Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the mouse model is generally less stable, resulting in notable variations in results. Here, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion. We share the lessons and experiences gained from our laboratory in the past decade. We further discuss the technical issues that account for the variability of this model and offer relevant solutions, which may help other investigators to establish a well-controlled, reliable animal model of ischemic AKI.

show abstract

“…Furthermore, RGS4 inhibited apoptosis of human umbilical vein endothelial and HEK293 cells . Previous research also reported that RGS4 deficiency promoted apoptosis in renal injury caused by ischemia and reperfusion . We determined that miR‐21‐3p targeted and negatively regulated RGS4.…”

Section: Discussionmentioning

confidence: 77%

MiR‐21‐3p modulates lipopolysaccharide‐induced inflammation and apoptosis via targeting TGS4 in retinal pigment epithelial cells

Liu

Ran

2019

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the most common cause of blindness and visual impairment in the elderly. 1 AMD is characterized by accumulation of yellow crystal deposits and loss of central vision due to degenerative changes in the macula. The integrity of the retina is strongly related to retinal pigment epithelial cells, which maintain the local extracellular environment. Morphological and functional abnormalities of these cells can lead to AMD. 2 Inflammation and apoptosis also play central roles in the pathophysiology of AMD. 3,4 Determining appropriate treatment for AMD is an important endeavour to increase patient quality of life.MicroRNAs (miRs) are a class of noncoding RNAs that can inhibit or degrade genetic targets by binding to their 3ʹ untranslated regions (UTRs). MiRs play integral roles in numerous disease processes, including oxidase stress, inflammation, and apoptosis. 5 For AbstractAge-related macular degeneration (AMD) is a major reason of blindness in the elderly.MicroRNAs are implicated in various pathological processes, including inflammation and apoptosis. In this study, we aim to investigate the biological functions of miR- 21-3p in inflammation and apoptosis caused by lipopolysaccharide (LPS) in humanretinal pigment epithelial (ARPE-19) cells. The miR-21-3p inhibitor and mimic were transfected into ARPE-19 cells for 48 hours, followed by exposed to LPS (10 μg/mL) for 24 hours. The mRNA and protein expression of IL-6 and MCP-1 were measured using real-time PCR (RT-PCR) and enzyme-linked immunosorbent assays. Cell viability, apoptosis, caspase 3 activity, cleaved caspase-3 and cleaved-PARP protein levels were detected to evaluate the effects of miR-21-3p on apoptosis. Additionally, the target relationship between miR-21-3p and regulator of G-protein signalling 4 (RGS4) was verified by dual luciferase reporter assay. RT-PCR analysis demonstrated that LPS induced miR-21-3p expression. Inhibition of miR-21-3p reduced the mRNA and protein levels of IL-6 and MCP-1. Apoptosis, caspase-3 activity, and cleaved-caspase 3 and cleaved PARP protein levels were repressed by the miR-21-3p inhibitor.However, overexpression of miR-21-3p showed the opposite results. Furthermore, we identified that miR-21-3p directly targeted the 3ʹ untranslated region of RGS4.MiR-21-3p negatively regulated the expression of RGS4 both in mRNA and protein levels. Silencing RGS4 reduced the anti-inflammatory and anti-apoptotic effects of miR-21-3p inhibitor. Our results revealed that miR-21-3p inhibition targeted RGS4 to attenuate inflammatory responses and apoptosis caused by LPS in ARPE-19 cells. K E Y W O R D Sapoptosis, inflammation, MiR-21-3p, RGS4

show abstract

RGS4, a GTPase activator, improves renal function in ischemia–reperfusion injury

Cited by 23 publications

References 46 publications

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

CD47 Blockade Reduces Ischemia-Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

Mouse model of ischemic acute kidney injury: technical notes and tricks

MiR‐21‐3p modulates lipopolysaccharide‐induced inflammation and apoptosis via targeting TGS4 in retinal pigment epithelial cells

Contact Info

Product

Resources

About